Antibacterial and synergistic activity of a new 8-hydroxyquinoline derivative against methicillin-resistant Staphylococcus aureus.

Aim: To evaluate the antibacterial and synergistic effect of a new 8-hydroxyquinoline derivative (PH176) against MRSA. Materials & methods: PH176 activity was determined by broth microdilution against 38 Staphylococcus aureus clinical isolates. The antibacterial and synergistic effects with oxacillin and nitroxoline were evaluated by time-kill assays to five MRSA isolates. Toxicity was evaluated by in vitro and ex vivo models. Results: The MIC50 and MIC90 of PH176 were 16 and 32 µg/ml, respectively. The PH176 and nitroxoline led to a reduction in colony count for four isolates and the combination of PH176 and oxacillin acted synergically for three isolates. Furthermore, PH176 was determined to be noncytotoxic/nonirritant. Conclusion: These results demonstrate that PH176 has revealed promising results to be a potential candidate to treat MRSA infections.

High Levels of Resistance to Cephalosporins Associated with the Presence of Extended-Spectrum and AmpC ß-Lactamases in Escherichia coli from Broilers in Southern Brazil.

The clinical importance of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has increased steadily over the years. The presence of the blaTEM, blaSHV, and blaCTX-M genes in the environment has been recently recognized as an important issue in the dissemination of resistance to cephalosporins. Food animals are considered important vectors for transfer of ESBL genes from the environment to humans. The objective of this study was to characterize the ESBL genes (blaTEM, blaSHV, and blaCTX-M types) that were most prevalent among 343 ceftazidime-resistant E. coli isolates (17 batches from 12 different farms) obtained from cloacal swabs of broiler chicken in southern Brazil. The blaSHV, blaCTX-M, blaTEM, blaIMP-type, blaVIM-type, blaNDM-1, blaKPC-type, blaGES-type, blaOXA-48, and mcr-1 genes were evaluated by polymerase chain reaction. A total of 27 (7.9%) E. coli isolates were positive for ESBL genes as follows: 24 for blaCTX-M (23 blaCTX-M-2 Group and 1 blaCTX-M-8) and 3 for blaSHV (2 blaSHV-2a and 1 blaSHV-18). A random sample of 32 ceftazidime/cefotaxime-resistant isolates that were negative for ESBL genes were evaluated for the presence of blaCMY-2 and 24 (75%) tested positive. We detected the blaCMY-2 gene in isolates from all farms. All isolates positive for ESBL or blaCMY-2 are considered multidrug resistant (resistant to at least three antibiotic classes). Our results suggest that broiler chickens are an important reservoir of blaCMY-2 and ESBL genes, including blaSHV-2a, described for the first time in animals originating from Brazil in this study, and blaSHV-18, which has never been described in Brazil before. This fact highlights the importance of controlling the use of antibiotics in animal production to reduce environmental sources of resistance genes.

Synergy of polymyxin B, tigecycline and meropenem against carbapenem-resistant Enterobacter cloacae complex isolates.

Here, we evaluated the combinations of antibiotics polymyxin B (PMB), tigecycline (TGC) and meropenem (MEM) by time-kill curves (TKC) against carbapenem-resistant Enterobacter cloacae isolates. Combination of PMB/TGC and PMB/MEM showed promising results in sub-inhibitory concentration of PMB indicating the possibility of reducing the dose of PMB used in the treatment.

Rapid tools to gain insights into the interaction dynamics of new 8-hydroxyquinolines with few fungal lines.

The combination of tools such as time-kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8-hydroxy-5-quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8-hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time-kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time-kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non-irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.

Combined creatinine-cystatin C CKD-EPI equation significantly underestimates measured glomerular filtration rate in people with type 2 diabetes mellitus.

AIM: To evaluate the accuracy of creatinine and cystatin C (cysC) equations to estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) patients and healthy adults. METHODS: Case-control study including 84 patients with type 2 DM and 100 healthy adults with measured GFR (mGFR)≥60mL/min/1.73m2. GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement was evaluated by Bland & Altman analysis. RESULTS: Healthy individuals were 66% females, aged 38±14years; they presented mGFR 112±19mL/min/1.73m2 and eGFR by CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108±17, 102±15, 97±16 and 93±16mL/min/1.73m2. DM group were 50% females, aged 59±19years and presented mGFR 104±27 and eGFR 87±19, 80±18, 74±20 and 73±18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR, excepting creatinine-based CKD-EPI in the healthy group. The performance was considerably worse for GFRs above 120mL/min/1.73m2. CONCLUSION: In both healthy and type 2 DM patients, cystatin C-based equations, including the combined CKD-EPI creatinine-cystatin equation, failed to improve the accuracy of GFR estimation, especially for normal and high normal GFR values.

Vitamin D Deficiency Increases the Risk of Adverse Neonatal Outcomes in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. METHODS: 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. RESULTS: Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09-12.11) and for SGA was 4.32 (95%CI 1.75-10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. CONCLUSIONS: In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia.

Serum vitamin D insufficiency is related to blood pressure in diabetic pregnancy.

BACKGROUND: Vitamin D deficiency in pregnancy has been associated with an increased risk of preeclampsia. However, the association between serum vitamin D and blood pressure in pregnant women has been scarcely evaluated, particularly in women with a high risk of developing hypertensive disorders of pregnancy. We sought to evaluate the association between serum 25-hydroxyvitamin D and blood pressure in pregnant women with gestational diabetes mellitus (GDM). METHODS: A cohort of 184 pregnant women with GDM was followed during the third trimester of pregnancy and early puerperium. Blood pressure was recorded in all prenatal visits, and serum vitamin D was measured by chemiluminescence immunoassay. Pearson's coefficients and multiple linear regressions were used to study predictors of blood pressure levels. RESULTS: Women with vitamin D insufficiency (<30ng/mL; n = 159) had higher systolic and diastolic blood pressure than the remaining participants. In white women (n = 136), serum vitamin D levels presented a significant negative correlation with systolic blood pressure at the beginning (r = -0.268; P = 0.002) and at the end of the third trimester (r = -0.203; P = 0.02), and vitamin D significantly affected systolic blood pressure after adjusting for confounders. This was not observed in women of other ethnicities. CONCLUSIONS: In this cohort of pregnant women with GDM, vitamin D insufficiency was associated with higher blood pressure, and in white women, serum vitamin D was an independent predictor of systolic blood pressure during pregnancy.

Perfil lipídico e obesidade em homens de um município da Região Sul do Brasil / Lipid profile and obesity in men from a county of the South

Objetivos: Avaliar o perfil lipídico e sua relação com obesidade em homens de Flores da Cunha, Rio Grande do Sul.Métodos: Um estudo transversal de base populacional selecionou homens moradores do município de Flores da Cunha, localizado na região nordeste do Rio Grande do Sul. Informações sociodemográficas foram obtidas por meio de um questionário. A coleta de amostras de sangue foi feita em um centro de saúde a as análises bioquímicas foram realizadas no laboratório de Toxicologia do Centro Universitário Metodista do IPA. Resultados: Foram estudados 368 homens, cuja idade variou de 25 a 83 anos, com média de 49,3 anos. As análises bioquímicas mostraram os seguintes valores médios: colesterol total 211,3 mg/dL; triglicerídeos 178,3 mg/dL; colesterol HDL (high density lipoprotein ? lipoproteína de alta densidade) 46,4 mg/dL; e colesterol LDL (low density lipoprotein ? lipoproteína de baixa densidade) 132,4 mg/dL. Houve diferença significativa quando comparados os resultados dos triglicerídeos em grupos com índice de massa corporal (IMC) normal e obesos (p<0,001) e entre grupos com sobrepeso e obesos (p=0,001); o colesterol HDL diferiu entre grupos com IMC normal e sobrepeso (p<0,001) e entre IMC normal e obesos (p<0,001). Os indivíduos eutróficos apresentam os menores valores de triglicerídeos e os maiores de colesterol HDL.Conclusões: Os dados obtidos, com aproximadamente 80% da amostra apresentando excesso de peso e um percentual relevante apresentando níveis plasmáticos elevados de lipídios, causam preocupação, considerando a morbimortalidade a que estão ligados esses fatores.

Aims: To evaluate the lipid profile and its relationship with obesity in men from Flores da Cunha, Rio Grande do Sul.Methods: A population-based cross-sectional study included men living in the county of Flores da Cunha, located in northeastern Rio Grande do Sul, the southernmost state in Brazil. Sociodemographic data were obtained through aquestionnaire. Blood samples were taken at a health center and the biochemical analyzes were performed in the laboratoryof Toxicology of the Centro Universitário Metodista do IPA.Results: We studied 368 men whose ages ranged from 25 to 83 years, mean 49.3 years. Biochemical analysis showedthe following average values: total cholesterol 211.3 mg/dL, triglycerides 178.3 mg/dL, HDL (high density lipoprotein) cholesterol 46.4 mg/dL, and LDL (low-density lipoprotein) cholesterol 132.4 mg/dL. There were significant differenceswhen comparing results of triglycerides in body mass index (BMI) normal and obese subjects (p<0.001) and amongoverweight and obese groups (p=0.001). HDL cholesterol differed between groups with normal BMI and overweight(p<0.001) and between obese and normal BMI (p<0.001). The normal individuals had the lowest values of triglyceridesand higher HDL cholesterol.Conclusions: The data of approximately 80% of the sample presenting overweight and a relevant percentage presentingelevated plasma levels of lipids are cause for concern, considering the morbidity and mortality to which these factors are linked.